Both, common gene variants and human adenovirus 36 (Adv36) are involved in the pathogenesis of obesity. The potential relationship between these two pathogenic factors has not yet been investigated. The aim of our study was to examine the association of obesity susceptibility loci with Adv36 status. Genotyping of ten gene variants (in/near TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, FTO) and analysis of Adv36 antibodies was performed in 1,027 Czech adolescents aged 13.0-17.9 years. Variants of two genes (PCSK1 and BDNF) were associated with Adv36 seropositivity. A higher prevalence of Adv36 antibody positivity was observed in obesity risk allele carriers of PCSK1 rs6232, rs6235 and BDNF rs4923461 vs. noncarriers (χ2=6.59, p=0.010; χ2=7.56, p=0.023 and χ2=6.84, p=0.033, respectively). The increased risk of Adv36 positivity was also found in PCSK1 variants: rs6232 (OR=1.67, 95 % CI 1.11-2.49, p=0.016) and rs6235 (OR=1.34, 95 % CI 1.08-1.67, p=0.010). PCSK1 rs6232 and BDNF rs925946 variants were closely associated with Adv36 status in boys and girls, respectively (χ2=5.09, p=0.024; χ2=7.29, p=0.026). Furthermore, PCSK1 rs6235 risk allele was related to Adv36 seropositivity (χ2=6.85, p=0.033) in overweight/obese subgroup. In conclusion, our results suggest that obesity risk variants of PCSK1 and BDNF genes may be related to Adv36 infection., L. Dušátková, H. Zamrazilová, I. Aldhoon Hainerová, R. L. Atkinson, B. Sedláčková, Z. P. Lee, J. Včelák, B. Bendlová, M. Kunešová, V. Hainer., and Obsahuje bibliografii
Obesity in childhood increases the risk of obesity in adulthood and is predictive for the development of metabolic disorders. The fatty acid composition is associated with obesity and obesityassociated disorders. We investigated the relationship between serum fatty acids composition, adiposity, lipids profile, parameters of glucose metabolism and leptin. The study subjects were 380 adolescents aged 15.0-17.9 years. The study's variables included anthropometric measurements, levels of serum lipids and hormonal parameters. Individual fatty acids were determined in plasma by gas-liquid chromatography. Palmitoleic acid (16:1n-7, PA) significantly positively correlated with percentage of body fat. Saturated fatty acids in phospholipids (PL) positively correlated with BMI and percentage of body fat. PA content in all lipids classes positively correlated with total cholesterol (TC), HDL cholesterol, triglycerides (TG) levels. Stearoyl-CoA desaturase (SCD) activity positively correlated with percentage of body fat and positive correlations of SCD and PA level with leptin were found. Plasma PA content and SCD are associated with adiposity and leptin in obese adolescents. No significant correlation between PA level and insulin resistance was found. Palmitoleate positively correlated with TC, HDL cholesterol, TG and LDL cholesterol levels., P. Hlavaty, E. Tvrzicka, B. Stankova, H. Zamrazilova, B. Sedlackova, L. Dusatkova, V. Hainer, M. Kunesova., and Obsahuje bibliografii
Associations between different infectious agents and obesity have been reported in humans for over thirty years. In many cases, as in nosocomial infections, this relationship reflects the greater susceptibility of obese individuals to infection due to impaired immunity. In such cases, the infection is not related to obesity as a causal factor but represents a complication of obesity. In contrast, several infections have been suggested as potential causal factors in human obesity. However, evidence of a causal linkage to human obesity has only been provided for adenovirus 36 (Adv36). This virus activates lipogenic and proinflammatory pathways in adipose tissue, improves insulin sensitivity, lipid profile and hepatic steatosis. The E4orf1 gene of Adv36 exerts insulin senzitizing effects, but is devoid of its pro-inflammatory modalities. The development of a vaccine to prevent Adv36- induced obesity or the use of E4orf1 as a ligand for novel antidiabetic drugs could open new horizons in the prophylaxis and treatment of obesity and diabetes. More experimental and clinical studies are needed to elucidate the mutual relations between infection and obesity, identify additional infectious agents causing human obesity, as well as define the conditions that predispose obese individuals to specific infections., V. Hainer, H. Zamrazilová, M. Kunešová, B. Bendlová, I. Aldhoon-Hainerová., and Obsahuje bibliografii
The local concentration of glucocorticoids is intensively regulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD 1). Human 11β-HSD 1 also reversibly catalyzes the inter-conversion of 7α-hydroxy- and 7β-hydroxy-dehydroepiandrosterone (DHEA) into 7-oxo-DHEA. The cohort of 282 obese adolescents, 154 girls (median age 15.31 years, range 14.17-16.68 years) and 128 boys (median age 14.95 years, range 13.87-16.16 years), BMI (Body Mass Index) >90th percentile was examined. In samples collected before and after one month of reductive diet therapy, circulating levels of steroids were analyzed by liquid chromatography-tandem mass spectrometry and radioimmunoassay methods. The model of the treatment efficacy prediction was calculated. A significant reduction in circulating levels of cortisone, E2 and increased levels of 7β-hydroxy-DHEA after the reductive treatment was observed. Levels of cortisol, DHEA, DHT sustained without any significant change. The predictive Orthogonal Projections to Latent Structures (OPLS) model explained 20.1 % of variability of BMI, z-score change by the basal levels of 7α-hydroxy-DHEA, DHEA, cortisol and E2 as the strongest predictors. Reduced levels of circulating cortisone and reduced ratios of oxygenated/reduced metabolites reflect increased reductase activity of 11β-HSD 1 with reduced BMI, z-score. We hypothesize whether these changes can be attributed to the altered activity of 11β-HSD 1 in the liver., L. Máčová, L. Sosvorová, J. Vítků, M. Bičíková, M. Hill, H. Zamrazilová, B. Sedláčková, L. Stárka /., and Obsahuje bibliografii